S255: EFFICACY AND SAFETY OF TISAGENLECLEUCEL IN PEDIATRIC AND YOUNG ADULT PATIENTS (PTS) WITH RELAPSED OR REFRACTORY (R/R) MATURE B-CELL NON-HODGKIN LYMPHOMA (NHL): THE PHASE II BIANCA STUDY
Authors: V. Minard-Colin, J. Buechner, F. Locatelli, B. Gonzalez Martinez, B. J. Vormoor, S. Cooper, J. Krueger, S. Napolitano, A. Attarbaschi, A. Baruchel, S. Ghorashian, M. L. Hermiston, H. Hiramatsu, M. Ifversen, S. John, S. L. Khaw, T. A. O’Brien, C. L. Phillips, C. Diaz de Heredia, D. Tomizawa, K. Vettenranta, A. S. Wayne, S. Newsome, R. Awasthi, S. Redondo, A. Masood, S. L. Maude, B. Burkhardt
Journal: HemaSphere (2022)

Background: Chimeric antigen receptor (CAR)-T cell therapy (tx) targeting CD19 is approved for treatment of adult r/r large B-cell lymphoma (LBCL) and pediatric r/r B-cell acute lymphoblastic leukemia (ALL). Pediatric and young adult pts with r/r mature B-NHL have dismal prognoses, especially those with Burkitt lymphoma (BL), and limited clinical benefit from available tx. Aims: Herein we report primary efficacy and safety outcomes from the global, multicenter, open-label, single-arm Phase II BIANCA trial (NCT03610724). Methods: Pts ≤25 y and ≥6 kg at screening with histologically confirmed CD19+ r/r mature B-NHL after ≥1 prior lines of tx were eligible following successful leukapheresis. Pts received optional bridging chemotherapy and fludarabine/cyclophosphamide or cytarabine/etoposide for lymphodepletion prior to a single intravenous injection of tisagenlecleucel (target dose range, 0.2-5x106/kg bodyweight [pts ≤50 kg] or 0.1-2.5x108 [pts >50 kg] CAR+ viable T cells). The primary endpoint was overall response rate (ORR=complete response [CR]+partial response [PR]) by local investigator assessment in the efficacy analysis set (EAS), which excludes pts with pre-infusion CR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and CAR-T cell kinetics. Results: As of October 10, 2021, 33/34 pts enrolled received tisagenlecleucel (EAS, N=28). Median age was 13 y (range, 3-22 y), 70% were male, 55% had BL, and 45% had LBCL. Pts received a median of 2 prior tx (18% received prior stem cell transplant [SCT]), 85% had stage III/IV disease at initial diagnosis, 15% were primary refractory, 30% were refractory, and 55% had relapsed/progressed at study entry. Median time from enrollment to infusion was 35 d (range, 7-62 d). Median time from tisagenlecleucel infusion to data cutoff was 16 mo (range, 6-30 mo). Bridging chemotherapy was given to 94%. ORR was 32% (95% CI: 15.9-52.4); 7% had a CR. Subgroup analysis suggested that pts with BL had a lower ORR than pts with LBCL (20% vs 46%). Median PFS was 2.5 mo (95% CI: 1.1-2.9); median OS was 11.4 mo (95% CI: 3.4-not estimable); 12-mo estimated PFS and OS were 23% (95% CI: 8.9-40.3) and 47% (95% CI: 26.6-65.0), respectively. Of the 18 BL pts, 7 (39%) are alive post infusion (1 received allogeneic SCT, 1 surgery, 3 other tx, and 2 no other tx). There were no tx-related deaths; most tx-related grade (gr) ≥3 (94%) and serious (52%) adverse events occurred ≤8 w post infusion. A neurologic event (NE) occurred in 27%; 15% had a gr ≥3 NE, and none had gr 5 NE. Cytokine release syndrome (CRS; per Lee 2014 criteria) occurred in 70%, 9% had gr 3 CRS, and there was no gr ≥4 CRS. Median time to CRS onset and duration were 6 d (range, 1-27 d) and 5 d (range, 1-13 d), respectively. Only 1 pt died ≤30 d post infusion, due to disease progression. Geometric mean maximal expansion (Cmax) across all pts was 5730 copies/μg, and median time to Cmax was 12.8 d (range, 2.5-21.9 d) by qPCR. Median CAR-T cell persistence in pts with CR or PR was 182 d (range, 20.9-562 d). Image:Summary/Conclusion: Tisagenlecleucel demonstrated efficacy in pediatric and young adult pts with r/r mature B-NHL and comparable safety to that recorded in adults with DLBCL. The OS is encouraging; however, optimal positioning of tisagenlecleucel in the treatment of pediatric r/r B-NHL requires further exploration, especially for BL, which is highly aggressive and challenging to treat in the relapse setting.